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Functional domains and the antiviral effect of the double-stranded RNA-dependent protein kinase PKR from Paralichthys olivaceus
Zhu, Rong; Zhang, Yi-Bing; Zhang, Qi-Ya; Gui, Jian-Fang; Gui, JF, Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Grad Sch, Wuhan 430072, Peoples R China
2008-07-01
Source PublicationJOURNAL OF VIROLOGY
ISSN0022-538X
Volume82Issue:14Pages:6889-6901
AbstractThe double-stranded RNA (dsRNA)-dependent protein kinase PKR is thought to mediate a conserved antiviral pathway by inhibiting viral protein synthesis via the phosphorylation of the alpha subunit of eukaryotic initiation factor 2 (eIF2 alpha). However, little is known about the data related to the lower vertebrates, including fish. Recently, the identification of PKR-like, or PKZ, has addressed the question of whether there is an orthologous PKR in fish. Here, we identify the first fish PKR gene from the Japanese flounder Paralichthys olivaceus (PoPKR). PoPKR encodes a protein that shows a conserved structure that is characteristic of mammalian PKRs, having both the N-terminal region for dsRNA binding and the C-terminal region for the inhibition of protein translation. The catalytic activity of PoPKR is further evidence that it is required for protein translation inhibition in vitro. PoPKR is constitutively transcribed at low levels and is highly induced after virus infection. Strikingly, PoPKR overexpression increases eIF2 alpha phosphorylation and inhibits the replication of Scophthalmus maximus rhabdovirus (SMRV) in flounder embryonic cells, whereas phosphorylation and antiviral effects are impaired in transfected cells expressing the catalytically inactive PKR-K421R variant, indicating that PoPKR inhibits virus replication by phosphorylating substrate eIF2 alpha. The interaction between PoPKR and eIF2 alpha is demonstrated by coimmunoprecipitation assays, and the transfection of PoPKR-specific short interfering RNA further reveals that the enhanced eIF2 alpha phosphorylation is catalyzed by PoPKR during SMRV infection. The current data provide significant evidence for the existence of a PKR-mediated antiviral pathway in fish and reveal considerable conservation in the functional domains and the antiviral effect of PKR proteins between fish and mammals.; The double-stranded RNA (dsRNA)-dependent protein kinase PKR is thought to mediate a conserved antiviral pathway by inhibiting viral protein synthesis via the phosphorylation of the alpha subunit of eukaryotic initiation factor 2 (eIF2 alpha). However, little is known about the data related to the lower vertebrates, including fish. Recently, the identification of PKR-like, or PKZ, has addressed the question of whether there is an orthologous PKR in fish. Here, we identify the first fish PKR gene from the Japanese flounder Paralichthys olivaceus (PoPKR). PoPKR encodes a protein that shows a conserved structure that is characteristic of mammalian PKRs, having both the N-terminal region for dsRNA binding and the C-terminal region for the inhibition of protein translation. The catalytic activity of PoPKR is further evidence that it is required for protein translation inhibition in vitro. PoPKR is constitutively transcribed at low levels and is highly induced after virus infection. Strikingly, PoPKR overexpression increases eIF2 alpha phosphorylation and inhibits the replication of Scophthalmus maximus rhabdovirus (SMRV) in flounder embryonic cells, whereas phosphorylation and antiviral effects are impaired in transfected cells expressing the catalytically inactive PKR-K421R variant, indicating that PoPKR inhibits virus replication by phosphorylating substrate eIF2 alpha. The interaction between PoPKR and eIF2 alpha is demonstrated by coimmunoprecipitation assays, and the transfection of PoPKR-specific short interfering RNA further reveals that the enhanced eIF2 alpha phosphorylation is catalyzed by PoPKR during SMRV infection. The current data provide significant evidence for the existence of a PKR-mediated antiviral pathway in fish and reveal considerable conservation in the functional domains and the antiviral effect of PKR proteins between fish and mammals.
SubtypeArticle
KeywordInitiation Factor-ii Translational Control Molecular-cloning Binding Domains Cab Cells Eukaryotic Initiation-factor-2-alpha Messenger-rnas Alpha-subunit Interferon Virus
Department[Zhu, Rong; Zhang, Yi-Bing; Zhang, Qi-Ya; Gui, Jian-Fang] Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Grad Sch, Wuhan 430072, Peoples R China
Subject AreaVirology
DOI10.1128/JVI.02385-07
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
Indexed BySCI
Language英语
WOS Research AreaVirology
WOS SubjectVirology
WOS IDWOS:000257545300011
WOS KeywordINITIATION FACTOR-II ; TRANSLATIONAL CONTROL ; MOLECULAR-CLONING ; BINDING DOMAINS ; CAB CELLS ; EUKARYOTIC INITIATION-FACTOR-2-ALPHA ; MESSENGER-RNAS ; ALPHA-SUBUNIT ; INTERFERON ; VIRUS
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Document Type期刊论文
Identifierhttp://ir.ihb.ac.cn/handle/152342/8062
Collection期刊论文
Corresponding AuthorGui, JF, Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Grad Sch, Wuhan 430072, Peoples R China
AffiliationChinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Grad Sch, Wuhan 430072, Peoples R China
Recommended Citation
GB/T 7714
Zhu, Rong,Zhang, Yi-Bing,Zhang, Qi-Ya,et al. Functional domains and the antiviral effect of the double-stranded RNA-dependent protein kinase PKR from Paralichthys olivaceus[J]. JOURNAL OF VIROLOGY,2008,82(14):6889-6901.
APA Zhu, Rong,Zhang, Yi-Bing,Zhang, Qi-Ya,Gui, Jian-Fang,&Gui, JF, Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Grad Sch, Wuhan 430072, Peoples R China.(2008).Functional domains and the antiviral effect of the double-stranded RNA-dependent protein kinase PKR from Paralichthys olivaceus.JOURNAL OF VIROLOGY,82(14),6889-6901.
MLA Zhu, Rong,et al."Functional domains and the antiviral effect of the double-stranded RNA-dependent protein kinase PKR from Paralichthys olivaceus".JOURNAL OF VIROLOGY 82.14(2008):6889-6901.
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